The expression of retinoic acid receptors and the effects in vitro by retinoids in human pancreatic cancer cell lines

INTRODUCTION: Analogues of vitamin A have been shown to influence growth of malignant tissue, such as pancreatic cancer. AIMS: To study the expression of retinoic acid receptors (RAR) in pancreatic cancer cells and the effect of three different retinoids on the cell number in vitro were studied. METHODOLOGY: Cell lines were established from 13 patients who underwent surgery for pancreatic adenocarcinoma. The expression of the retinoic acid receptors (RAR) and retinoic X receptor (RXR) subtypes (alpha, beta, and gamma) was studied with western blotting and specific antibodies. The effect of incubation with all-trans-retinoic acid (atRA; tretinoin), 9-cis-retinoic acid (9-cis-RA), and 13-cis-retinoic acid (13-cis-RA; isotretinoin) on the cell number was examined with use of a Roche XTT cell proliferation kit. RESULTS: The RXRalpha receptor was expressed in all cell lines. RARalpha,beta and RXRbeta were expressed in most of them. RXRgamma was expressed in about half of the cell lines and RARgamma in only one. Incubation of the cells with retinoids showed a decreased cell number at concentrations of 104 M, except for 9-cis-RA, to which only about half of the cell lines responded. CONCLUSION: Two or more of the RAR subtypes were expressed in each pancreatic cell line. There was no uniform pattern of receptor expression; however, the cell lines responded with decreased cell number to high concentrations of atRA and 13-cis-RA but not to 9-cis-RA. (Less)